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The first known assignment of the U.S.S. was the order placed for the assassination of Dr. James Marcus. Increasingly paranoid over Marcus's research, Oswell E. Spencer ordered his colleague's execution.[2] While not sporting their later comrades' trademark gas masks, the unit did share similar tactics employed in September 1998, namely having agents operate in two-man cells. The use of the MP5 submachine-guns as primary weapons was also echoed by later units.

The next confirmed implementation of the U.S.S. was on July 23, 1998. Albert Wesker, an Umbrella researcher, former security officer, and current (at the time) police infiltrator, was tasked with the re-opening of the Umbrella Executive Training Center,[3] which had been abandoned since Marcus' death. With both the first and second investigation units compromised by an unexpected t-Virus outbreak, along with the Ecliptic Express (a private intercity train ready to take Umbrella personnel for management training), the U.S.S.' "Delta Team" was called in to investigate. Following Wesker's orders, the two-man team took control of the engine and started it up again. When the team reported back in to Wesker, the train was ten minutes away from the training facility's station. However, they were ambushed and infected by a horde of infected leeches. The operatives would transform into zombies minutes later.

Later that year, in September, Umbrella became concerned over Dr. William Birkin's development of the G-virus, a muta genic toxin set to replace the t-Virus. Intent on selling the virus over to the U.S. Government for military applications, the U.S.S. was quickly called in to Raccoon City to intervene in any proceedings. On September 20, police officer Carl Nielson filed a report after encountering an individual skulking through the sewers. Although unable to catch up to the man to question him, Officer Nielson did stumble onto military-grade weaponry such as C4 plastic explosives with a detonator, and a broken infra-red scope for customizing firearms.[4]

Not long after, the two-man "Alpha Team", lead by "HUNK", trapped Birkin in his lab. With orders to retrieve a sample of the virus, the U.S.S. unit gunned down Dr. William Birkin and left with samples of the G-Virus (HUNK is actually seen here calling in the success of the mission). Leaving in a hurry to avoid detection, the two failed to notice Birkin carrying another sample of "G". Injecting it into himself, he revived himself from near death and mutated into a frightening monster ready to enact his revenge. Several U.S.S. teams in the sewers, composed of at least eight men, were swiftly executed by the renegade doctor, with HUNK barely escaping alive.

Fully regaining consciousness on September 30, HUNK made his way out of the sewers and to the Raccoon City Police Department's helipad and successfully escaped the city.

On the last day of the outbreak, the 2nd U.S.S. Squad was tasked with removing the experimental weapon Nyx from the city, operating from Main Street. The commander, Rodriguez, went rogue and attempted to steal the bio-weapon instead and offered refuge to a rouge researcher named Linda and a few survivors aiding her. A UBCS team under the command of Arnold and under the supervision of Umbrella Executive Tommy Neilson was dispatched to kill him and retrieve the stolen B.O.W. Despite the nearby area being mined, Rodriguez escaped by helicopter, but lost Nyx in the process. The rest of the squad was killed and scattered around the nearby area as zombies sometime before these events.

The last known official deployment of the U.S.S. was in November 1998, when a small U.S.S. team lead by HUNK was assigned to transport a container to Rockfort Island. The mission was controversial in that Alfred Ashford, the island base's commander, did not reveal to the team exactly what was inside the crate - HUNK was concerned over the danger of an unidentified package that could have put him and the rest of his unit in danger.

During the December 1998 attack on Rockfort by spies associated with a rival organization, the Umbrella Special Forces trainees were caught up in the fighting, with those who weren't killed by the enemy agents being infected by the t-Virus.[notes 1]

The standard weapon used by the U.S.S. in Resident Evil 2 is the Heckler & Koch MP5 Sub-Machine Gun. Although they have been known to use other weapons such as pistols, with HUNK having his own special handgun, which he nicknamed Matilda.

In Resident Evil: The Darkside Chronicles, the U.S.S. standard MP5 is replaced with the Steyr TMP. Also, judging by the inscription on the barrel of the Custom Magnum Parts found in Resident Evil 2, the U.S.S.'s armory also contained some heavy, albeit impractical firepower; a 10-inch version of the IMI Desert Eagle semi-automatic magnum handgun chambered in .50 Action Express—when or where it could have seen operative use is unknown.

U.S.S. 2nd Squad leader Rodriguez is seen with a Remington M870 in concept art, although he holds an M4 during gameplay.